Early observations that X-irradiation and nitrogen mustard were mutagenic first raised the concern of geneticists to the potential dangers of physical and chemical agents in the environment and sparked intensive inquiries into the nature of the mutagenesis process. Recent studies of this phenomenon have relied heavily on microbial systems but have been very successful in detailing both the molecular nature of alterations to the genetic material and the enzymatic nature of the genetic control of DNA repair mechanisms. These latter observations have, in large measure, depended upon the use of genetically-altered mutagen-sensitive strains and recent observations with eucaryotes suggest that mutagen-sensitive strains will be similarly useful in advancing our knowledge of these processes in higher organisms. This proposal describes studies aimed at developing and testing new genetic strains of the complex multicellular eucaryote, Drosophila melanogaster, which will be useful tools in the evaluation of environmental chemicals for potential mutagenic activity. The experiments have been designed to assay the entire Drosophila genome in order to isolate mutant strains which exhibit sensitivity or resistance to particular chemical agents, especially mutagens. Such strains will undergo genetic and biochemical characterizations for deficiencies in DNA repair to determine their feasibility as test strains for the evaluation of the mutagenic potential of environmentally important compounds. One example of the potential usefulness of such strains involves studies with the compound 2,2-dichlorovinyl dimethyl phosphate (DDVP), the active constituent of a widespread household insecticide, "dichlorvos". DDVP has been shown to alkylate DNA but there have been conflicting reports concerning its mutagenicity. Recent studies with mutagen-sensitive DNA repair- deficient E, coli. strains confirmed its mutagenicity and likened its mechanism of action to that observed with the monofunctional alkylating agent, MMS. Preliminary experiments in our laboratory have succeeded in isolating an MMS-sensitive strain of Drosophila and a test of DDVP mutagenicity in this strain should tell us if potential environmental hazards for multicellular eucaryotes will be encountered with widespread environmental use of this insecticide.